【摘要】 [目的]评估肺泡灌洗液(BALF)中SHOX2和RASSF1A基因甲基化联合检测(任意阳性)在肺癌诊断中的临床价值。[方法]收集经病理确诊的580例患者,其中肺癌261例,良性肺部疾病293例,非肺部的恶性肿瘤26例。将良性肺部疾病和非肺部的恶性肿瘤患者共319例作为对照组。对全部580例患者的BLAF样本,采用实时荧光PCR(RT-PCR)与测序法检测BALF中SHOX2和RASSF1A两种基因甲基化情况,比较两种检测方法的一致性。以病理诊断为金标准,对277例具有细胞学结果的患者(肺癌组130例,对照组147例),比较采用RT-PCR法SHOX2和RASSF1A基因甲基化检测与细胞学检测对肺癌诊断的敏感性和特异性。[结果]RT-PCR法与测序法两种方法检测580例患者BLAF样本SHOX2基因和RASSF1A基因甲基化结果的一致率分别是97.5%和98.0%。580例BLAF样本采用RT-PCR法检测SHOX2和RASSF1A基因甲基化任意阳性对肺癌诊断的敏感性和特异性分别是74.3%和87.1%。在277例有细胞学结果的患者中,RT-PCR法SHOX2和RASSF1A基因甲基化检测任意阳性对肺癌诊断的敏感性和特异性分别为83.2%和92.5%,与细胞学检测(44.6%和98.6%)相比,敏感性显著提高,但特异性有所降低,差异均有统计学意义(P<0.01,P<0.05)。基因甲基化联合检测(任意阳性)阳性率在细胞学发现癌细胞组为98.2%(57/58),结果未明组为100.0%(35/35),未发现癌细胞组为37.8%(14/37)。[结论]采用RT-PCR法进行BALF中SHOX2和RASSF1A基因甲基化联合检测,可以作为肺癌细胞学检查的补充,特别是在细胞学检测结果未明或阴性时。更多还原

【Abstract】 [Objective] To evaluate the application of combined detection of SHOX2 and RASSF1 A gene methylation in bronchoalveolar lavage fluid(BALF) for diagnosis of lung cancer. [Methods]BLAF samples and the pathological data were collected from 261 patients with lung cancer and 319 controls. The methylation statues of SHOX2 and RASSF1 A genes in BALF were detected by quantified real-time PCR(RT-PCR) and sequencing,and the consistency of two methods was analyzed. The sensitivity and specificity of either positive SHOX2 or RASSF1 A methylation for diagnosis of lung cancer were compared with cytological examination in 277 patients with cytological results(130 cases in lung cancer group,147 controls). [Results] The consistency rates of SHOX2 and RASSF1 A gene methylation detected by RT-PCR and sequencing were 97.5% and 98.0%,respectively. The sensitivity and specificity of combined positive SHOX2 and RASSF1 A methylation for diagnosis of lung cancer in 580 BALF samples detected by RT-PCR were 74.3% and 87.1%,respectively. In 277 cases with cytological results,the sensitivity of combined detection of SHOX2 and RASSF1 A methylation for diagnosis of lung cancer detected by RT-PCR was 83.2%,higher than that in cytological detection(44.6%,P<0.01); and the specificity in gene methylation(92.5%) was lower than that in cytological detection(98.6%,P<0.05). The positive rate of combined SHOX2 and RASSF1 A gene methylation was 98.2%(57/58)in cytology positive group,100.0%(35/35) in cytology undetermined group,and 37.8%(14/37)in cytology negative group. [Conclusion] Combination detection of methylation of SHOX2 and RASSF1 A genes in BALF by RT-PCR may be used as a supplement to cytology for diagnosis of lung cancer,especially in patients with undetermined or negative cytology.更多还原